The research proposed in this application is intended to elucidate the molecular mechanisms whereby B cell behavior is modified by signals which include interaction with antigen presented on a macrophage membrane. The possibility of "fine-tuning" clonal selection by changing the physical profile of presented antigen is of particular interest. The specific aims concern the use of fluid, synthetic, haptenated membrane structures (liposomes) as macrophage analogues, in whole mouse spleen or T- and/or macrophage-depleted cultures, to observe ways in which variation of liposomal properties such as quantity, epitope density, hapten valency, size and possibly charge and fluidity determine the type response given. Responses will be judged as to the extent of stimulation or tolerization of in vitro hapten-specific antibody-forming cell (AFC) induction. Control of induced antibody avidity and isotype by liposomal properties will also be investigated. Work concerning the in vitro, primary, IgM response will be continued and attempts to promote secondary and IgG responses to liposoms in vitro will also be made. Cellular requirements will be determined at each stage. A partial purification and characterization of factor(s) present in "Con A supernatants" which enable them to promote the response to liposomes by macrophage-depleted cultures is also planned. Immune dysfunction has been suspected of causing or promoting many of the diseases which remain uncontrollable. The work proposed here combines the disciplines of immunology and supramolecular structural chemistry in an attempt to discover basic principles controlling immune responses. It is anticipated that the results will permit prediction of conditions which would lead to immune dysfunction, and thus provide important clues as to faults which may exist in diseased states.